TABLE 2.

The biological activities of the chemical constituents of PPE.

NO.	Biological activity	PPE	Models	Dosage/Concentration	Conclusion	References
1	Antioxidant	Ellagic Acid	Cisplatin-Induced Nephrotoxicity Model On day 1, adult male Sprague-Dawley rats were intraperitoneally injected with cisplatin (7 mg/kg body weight (mg/kg BW))	From days 1–10, ellagic acid dissolved in corn oil was administered intraperitoneally at a dose of 10 mg/kg BW daily. At the end of the experiment, blood samples were collected from the rats	Ellagic acid exhibited protective effects against cisplatin-induced nephrotoxicity and oxidative stress in rats, potentially due to its potent scavenging activity against superoxide anions and hydroxyl radicals	Ateşşahín et al. (2007)
2			2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)-Induced Nephrotoxicity Model From days 11–13, male Wistar albino rats were injected daily with 15 μg/kg BW of TCDD dissolved in 0.15 mL of corn oil. At the end of the experiment, blood was collected via the jugular vein	From days 1–10, ellagic acid was administered orally at a dose of 10 mg/kg BW daily, dissolved in 0.15 mL of 50% dimethyl sulfoxide	Ellagic acid enhanced antioxidant capacity and prevented oxidative stress by maintaining Ca2+ homeostasis in HepG2 cells and inhibiting CYP1A1 activity, thereby providing protection against TCDD-induced nephrotoxicity	Padma et al. (2014)
3			High-Fat and High-Cholesterol Diet Model From weeks 1–8, 4-6-week-old New Zealand white rabbits with an average body weight of 1.5 kg were fed a diet enriched with 10% corn oil and 0.5% cholesterol	During the same period, rabbits were supplemented with 1% (w/w) ellagic acid. At the end of week 8, blood samples were collected via cardiac puncture	Ellagic acid demonstrated the ability to scavenge RO⋅ or ROO⋅ free radicals, inhibit the production of hydrogen peroxide and singlet oxygen, and suppress lipid peroxidation, thereby improving atherosclerosis	Yu et al. (2005)
4		Punicalagin	Lipopolysaccharide-induced testicular oxidative stress injury model: Day 1–7, adult male ICR mice were injected daily with lipopolysaccharide (600 μg/kg BW)	Day 1–7, mice were orally administered punicalagin at a dose of 9 mg/kg BW daily via gavage. On the last day of treatment, male mice were exposed to female mice for 4 days, followed by dissection and examination	Punicalagin significantly reduced the production of the strong oxidant NO and mitigated oxidative stress in the testes by activating nuclear factor erythroid 2-related factor 2 (Nrf2), reducing oxidative damage, and increasing sperm count	Rao et al. (2016)
5			CCl4-induced liver injury model: In the 5th week, mice were intraperitoneally injected with 0.07% CCl4 (v/v, 0.1 mL/100 g), and blood and liver tissue samples were collected 16 h later	After a 1-week adaptation period, mice were gavaged daily with punicalagin dissolved in distilled water (80 mg/kg BW) for 4 consecutive weeks	Punicalagin alleviated oxidative stress by increasing liver superoxide dismutase (SOD), glutathione peroxidase (GPx) activity, and Nrf2 protein expression, thereby protecting against CCl4-induced liver injury	Luo et al. (2019)
6		Quercetin	3-Nitropropionic acid (3-NPA)-induced oxidative stress model: Day 1–42, SPF-grade female mice were injected daily with 3-NPA (20 mg/kg BW)	Day 1–42, mice were intraperitoneally injected with quercetin (200 mg/kg BW)	Quercetin alleviated oxidative stress in this model by promoting SIRT1 expression, activating the SIRT1/ROS/AMPK signaling pathway, inhibiting ROS accumulation induced by oxidative stress, regulating autophagy levels, reducing cell apoptosis, and ultimately restoring ovarian function	Duan et al. (2024)
7			Xenoestrogen bisphenol S (BPS)-induced behavioral change model in zebrafish: From day 1 to day 21, adult zebrafish were placed in a 15-L aquarium with a BPS concentration of 20.52 M	From day 1 to day 21, quercetin was added to the aquarium water at a concentration of 2.96 M	Quercetin alleviated oxidative stress and behavioral changes induced by BPS by increasing GSH levels and superoxide dismutase activity, while reducing elevated lipid peroxidation in the zebrafish brain	Ragunath et al. (2022)
8		Catechin	Chronic unpredictable mild stress (CUMS) depression model constructed by external stressors: From week 1 to week 8, male Sprague Dawley rats were subjected daily to various stressors such as food deprivation, water deprivation, tail clipping, electric shock, and forced swimming	From week 1 to week 8, catechin hydrate (50 mg/kg BW) was orally administered daily	After catechin treatment, antioxidant parameters such as catalase, glutathione, and superoxide dismutase levels were restored, reversing CUMS-induced depression in rats by alleviating oxidative stress	Rai et al. (2019)
9		Protocatechuic acid	Isoproterenol-induced heart failure model in mice: From day 1 to day 14, C57BL/6NTac mice were intraperitoneally injected with isoproterenol (80 mg/kg BW) to construct a heart failure model	From day 6 to day 14, mice were injected daily with protocatechuic acid (100 mg/kg BW)	Kynurenine-3-monooxygenase (Kmo) was identified as a potential target of protocatechuic acid. Protocatechuic acid prevented heart failure by reducing ROS production induced by isoproterenol both in vivo and in vitro through Kmo downregulation	Bai et al. (2023)
10		Gallic acid	3-Nitropropionate acid (3-NP)-induced ovarian oxidative stress model in mice: From day 7 to day 16, female ICR mice were intraperitoneally injected with 3-NP (12.5 mg/kg BW) twice daily	Mice were administered gallic acid via oral gavage	Gallic acid exerted its protective effects by increasing antioxidant enzyme activity and reducing the mRNA expression levels of pro-apoptotic genes (Bim and Caspase-3), thereby inhibiting apoptosis in ovarian granulosa cells	Li et al. (2017)
11	Anti-inflammatory	Ellagic acid	Acute liver injury model induced by Lipopolysaccharide/d-Galactosamine (LPS/GalN) in Mice: Mice were intraperitoneally injected with GalN (800 mg/kg BW) and LPS (50 μg/kg BW), dissolved in PBS. After treatment, the mice were sacrificed	One hour prior to LPS/GalN administration, ellagic acid was injected intraperitoneally	Ellagic acid significantly suppressed the production of pro-inflammatory cytokines such as TNF-α and effectively inhibited Nuclear Factor-kappa B (NF-κB) activation by preventing the phosphorylation of IκB-α and NF-κB p65. This reduced inflammation and prevented liver injury	Gu et al. (2014)
12		Punicalagin	Pelvic inflammatory disease (PID) model in rats: A PID model was constructed by implanting a mixed microbial solution of Escherichia coli and Staphylococcus aureus into the rat cervix. On days 1–7, female Sprague Dawley rats were injected with 10 mg of progesterone. On days 9, 11, 13, and 15, gelatin sponges soaked in a nutrient broth containing E. coli and S. aureus were implanted into the cervical region	Rats were divided into preventive and therapeutic groups. The preventive group was administered punicalagin via gavage 1 day before PID induction, while the therapeutic group received punicalagin via gavage 1 day after confirming the PID model	In both groups, punicalagin significantly reduced IL-1β levels, lipid peroxidation, and catalase activity. It also decreased local leukocyte infiltration and oviduct fibrosis, demonstrating its potential as a safe and effective treatment for PID.	Zoofeen et al. (2024)
13			Collagen-induced arthritis (CIA) model in mice: On day 1, DBA/1 male mice were injected intradermally at the base of the tail with 200 mg of bovine type II collagen emulsified in a 1:1 ratio with complete Freund’s adjuvant to induce an initial immune response. On day 22, an immunization booster was administered with bovine type II collagen emulsified in incomplete Freund’s adjuvant (1:1)	From day 23 to day 37, punicalagin (50 mg/kg BW) was intraperitoneally injected daily	Punicalagin significantly reduced serum levels of IL-6 and TNF-α in CIA mice, alleviated cellular infiltration, synovial hyperplasia, cartilage destruction, and limb swelling, showing strong anti-arthritis effects	Huang et al. (2021)
14		Corilagin	Acute lung injury (ALI) model induced by Lipopolysaccharide (LPS) in mice: C57BL/6 mice were intratracheally instilled with LPS (2.5 μg/g BW) dissolved in PBS.	After 30 min of LPS stimulation, corilagin (10 mg/kg BW) was administered, and the mice were anesthetized and sacrificed 6 h later	Corilagin significantly reduced inflammatory cell infiltration in lung tissues and inhibited the production of pro-inflammatory cytokines TNF-α, IL-6, and IL-1β, thereby providing effective protection against LPS-induced ALI.	Liu F. C. et al. (2022)
15		Quercetin	Osteoarthritis (OA) model induced by monosodium iodoacetate (MIA) in rats: On day 1, male Sprague-Dawley rats were given a single intra-articular injection of 1 mg MIA into the right knee joint	From day 1 to day 28, rats were gavaged with quercetin daily	Quercetin significantly reduced serum levels of inflammatory cytokines, including IL-5, IL-6, IL-7, IL-10, and TNF-α, in OA rats. It also inhibited the expression of MMP-3, MMP-13, ADAMTS4, and ADAMTS5, reducing cartilage matrix degradation and demonstrating excellent anti-inflammatory and chondroprotective effects	Wang et al. (2023)
16		Catechin	Establishment of a coronary heart disease (CHD) model in rats using a high-fat diet and pituitrin injection: From weeks 1–10, 10-week-old SPF-grade Wistar rats were fed a high-fat diet. Forty-eight hours after the last feeding, the rats were intraperitoneally injected with pituitrin (30 U/kg BW) once daily for two consecutive days	Following the pituitrin injections, the rats were administered catechin via gavage once daily for 4 weeks	catechin significantly reduced levels of inflammatory biomarkers and cytokines such as C-reactive protein, Lp-PLA2, IL-6, and TNF-α. It also activated anti-inflammatory and protective signaling molecules such as Farnesoid X Receptor, STAT-3, and PKB/Akt, effectively improving the pathological state of CHD.	Tu et al. (2018)
17		Kaempferol	Establishment of a mouse asthma model using ovalbumin (OVA): On days 1 and 15, BALB/c mice were subcutaneously injected with 20 μg of OVA to induce sensitization. From days 29–31, the mice were exposed to 5% OVA aerosol for 20 min daily to establish the asthma model	During days 29–31, the mice were orally administered 0.1 mL of kaempferol solution (10 or 20 mg/kg BW) daily	Kaempferol inhibited the production of macrophage inflammatory protein-2 and the overexpression of its receptor CXCR2. It also modulated the Tyk2-STAT1/3 signaling pathway in response to IL-8, thereby alleviating airway inflammation	Gong et al. (2013)
18		Methyl gallate	Establishment of a hyperuricemia nephropathy (HN) model in mice using potassium oxide (PO): From days 1–28, male C57BL/6 mice were intraperitoneally injected daily with 300 mg/kg BW of PO.	Thirty minutes prior to each PO injection, the mice were administered methyl gallate via gavage	Methyl gallate significantly reduced levels of NLRP3, ASC, IL-1β, and caspase-1 proteins in HN mice. It effectively inhibited the activation of the NLRP3 inflammasome, thereby exerting renal protective effects against PO-induced HN.	Liu et al. (2021)
19	Antibacterial	Ellagic acid	Establishment of a mouse H. pylori Infection Model using H. pylori Strain (Sydney Strain 1): To establish the model, male C57BL/6 mice were orally administered 0.2 mL of bacterial suspension (108 CFU/mL) three times at 2-day intervals using a gavage tube	Two weeks after bacterial infection, the mice were administered ellagic acid (10 mg/kg BW) daily for 1 week via gavage	Ellagic acid restored and repaired gastric mucosal damage caused by H. pylori, demonstrating significant anti-H. pylori effects	De et al. (2018)
20			Establishment of a mouse Aeromonas hydrophila infection model: Male MF1 albino mice were fed a bacterial suspension of Aeromonas hydrophila (0.2 mL, 2 × 108 CFU) once a week for 2–4 weeks	The mice were administered ellagic acid via a stainless-steel gavage tube three times weekly (total dose 150 mg/kg BW) for 2–4 weeks	Ellagic acid treatment significantly increased levels of anti-LPS and anti-ECP IgM in infected mice, maintained the integrity of intestinal villi, and demonstrated antibacterial activity against Aeromonas hydrophila	Abuelsaad et al. (2013)
21		Kaempferol	An infection model was established by intraperitoneally inoculating C57BL/6 female mice with 5 × 106 CFU of the wild-type Listeria monocytogenes EGD strain	After infection, the mice were treated with kaempferol (100 mg/kg BW)	Kaempferol treatment significantly reduced the bacterial load in major target organs, such as the spleen, and improved the survival rate of infected mice by more than 20% on the 6th day post-infection, demonstrating strong anti-Listeria monocytogenes EGD activity	Wang et al., 2022)
22		Quercetin	Citrobacter rodentium-induced colitis model in mice: The colitis model was constructed by orally administering 2 × 108 CFU of Citrobacter rodentium culture to C57BL/6 mice, which were sacrificed on the 7th day post-infection	During weeks 1–2, quercetin (30 mg/kg BW) was supplemented in the mice’s basal rodent diet.	The mice showed no signs of colitis, and the colon’s bacterial populations, including Fusobacterium and Enterococcus, were suppressed, indicating that Quercetin exhibits antibacterial activity against Citrobacter rodentium	Lin et al. (2019)
23		Gallic acid	S. Typhimurium peritoneal infection model in mice: Mice were peritoneally infected with 1 × 106 CFU of S. Typhimurium	Starting 3 days before infection and continuing for 10 days after infection, mice were orally administered 100 μL of gallic acid (100 μg/mL BW) daily	Gallic acid treatment significantly increased the levels of cytokines such as IFN-γ, indicating that it might stimulate the host immune response. Infected mice showed a significant reduction in bacterial loads in organs such as the liver and a decrease in mortality, suggesting that the virulence of lethal-dose Typhimurium was attenuated. These results indicate that gallic acid effectively protects macrophages and mice from Typhimurium infection	Reyes et al. (2017)
24			B. abortus peritoneal infection model in mice: Mice were peritoneally infected with 2 × 104 CFU of B. abortus	Starting 3 days before infection and continuing for 14 days after infection, mice were orally administered 100 μg/mL BW of gallic acid daily	Gallic acid interfered with B. abortus invasion by inhibiting F-actin polymerization and downregulating mitogen-activated protein kinases (MAPKs). Additionally, it induced the secretion of protective cytokines such as IL-12, triggering a protective immune response and inhibiting bacterial proliferation in the spleen, demonstrating its antibacterial activity	Reyes et al. (2018)
25			Galleria mellonella (G. mellonella) infection model with multidrug-resistant escherichia coli: A multidrug-resistant Escherichia coli infection model was established by injecting 10 μL of a 2 × 106 CFU/mL bacterial suspension into the right fourth leg of G. mellonella larvae	One hour after infection, 10 μL of gallic acid was injected into the left fourth leg of the larvae	Gallic acid disrupted the bacterial outer and inner membranes and inhibited the mRNA expression of membrane permeability-related genes (e.g., acrA, acrB, tolC, acrD, and acrF), significantly improving the survival rate of Galleria mellonella. This demonstrates its antibacterial activity against multidrug-resistant Escherichia coli	Tian Q. et al. (2022)
26		Methyl gallate	An infection model was constructed by injecting 5 × 105 CFU of extensively drug-resistant P. aeruginosa into the hind leg of Galleria mellonella larvae	Two hours post-infection, the larvae were injected with methyl gallate	Methyl gallate significantly downregulated the expression of quorum-sensing-related genes in P. aeruginosa and dose-dependently improved the survival rate of the larvae. This demonstrates its antibacterial activity against extensively drug-resistant P. aeruginosa	Flores-Maldonado et al. (2024)